Platelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy

Atherosclerosis,the principle cause of cardiovascular disease(CVD)worldwide,is mainly characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris.Atherogenesis is associated with the upregulation of CD47,a key antiphagocytic molecule that is known to render malignant cells resistant to programmed cell removal,or“efferocytosis.”Here,we have developed platelet membrane-coated mesoporous silicon nanoparticles(PMSN)as a drug delivery system to target atherosclerotic plaques with the delivery of an anti-CD47 antibody.Briefly,the cell membrane coat prolonged the circulation of the particles by evading the immune recognition and provided an afinity to plaques and atherosclerotic sites.The anti-CD47 antibody then normalized the clearance of diseased vascular tissue and further ameliorated atherosclerosis by blocking CD47.In an atherosclerosis model established in ApoE^(-/-)mice,PMSN encapsulating anti-CD47 antibody delivery significantly promoted the efferocytosis of necrotic cells in plaques.Clearing the necrotic cells greatly reduced the atherosclerotic plaque area and stabilized the plaques reducing the risk of plaque rupture and advanced thrombosis.Overall,this study demonstrated the therapeutic advantages of PMSN encapsulating anti-CD47 antibodies for atherosclerosis therapy,which holds considerable promise as a new targeted drug delivery platform for efficient therapy of atherosclerosis。

Durable endothelium-mimicking coating for surface bioengineering cardiovascular stents

Mimicking the nitric oxide(NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis(ISR)effectively.However,the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx component.Herein,we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species(e.g.,Cu-DOTA coordination complex)and glycocalyx-like component(e.g.,heparin)to create a durable endothelium-mimicking surface.The stent surface was firstly coated with polydopamine(pDA),followed by a surface chemical cross-link with polyamine(pAM)to form a durable pAMDA coating.Using a stepwise grafting strategy,Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide chemistry.Owing to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules,this proposed strategy could provide 62.4%bioactivity retention ratio of heparin,meanwhile persistently generate NO at physiological level from 5.9±0.3 to 4.8±0.4×10^(-10) mol cm^(-2) min^(-1) in 1 month.As a result,the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis,inflammation,and intimal hyperplasia,enhanced re-endothelialization,and hence efficiently reduced ISR.

Photo-functionalized TiO_(2) nanotubes decorated with multifunctional Ag nanoparticles for enhanced vascular biocompatibility

Titanium dioxide(TiO2)has a long history of application in blood contact materials,but it often suffers from insufficient anticoagulant properties.Recently,we have revealed the photocatalytic effect of TiO2 also induces anticoagulant properties.However,for long-term vascular implant devices such as vascular stents,besides anticoagulation,also anti-inflammatory,anti-hyperplastic properties,and the ability to support endothelial repair,are desired.To meet these requirements,here,we immobilized silver nanoparticles(AgNPs)on the surface of TiO2 nanotubes(TiO2-NTs)to obtain a composite material with enhanced photo-induced anticoagulant property and improvement of the other requested properties.The photo-functionalized TiO2-NTs showed protein-fouling resistance,causing the anticoagulant property and the ability to suppress cell adhesion.The immobilized AgNPs increased the photocatalytic activity of TiO2-NTs to enhances its photo-induced anticoagulant property.The AgNP density was optimized to endow the TiO2-NTs with anti-inflammatory property,a strong inhibitory effect on smooth muscle cells(SMCs),and low toxicity to endothelial cells(ECs).The in vivo test indicated that the photofunctionalized composite material achieved outstanding biocompatibility in vasculature via the synergy of photo-functionalized TiO2-NTs and the multifunctional AgNPs,and therefore has enormous potential in the field of cardiovascular implant devices.Our research could be a useful reference for further designing of multifunctional TiO2 materials with high vascular biocompatibility.

A“built-up”composite film with synergistic functionalities on Mg-2Zn-1Mn bioresorbable stents improves corrosion control effects and biocompatibility

Control of premature corrosion of magnesium(Mg)alloy bioresorbable stents(BRS)is frequently achieved by the addition of rare earth elements.However,limited long-term experience with these elements causes concerns for clinical application and alternative methods of corrosion control are sought after.Herein,we report a“built-up”composite film consisting of a bottom layer of MgF2 conversion coating,a sandwich layer of a poly(1,3-trimethylene carbonate)(PTMC)and 3-aminopropyl triethoxysilane(APTES)co-spray coating(PA)and on top a layer of poly(lactic-co-glycolic acid)(PLGA)ultrasonic spray coating to decorate the rare earth element-free Mg-2Zn-1Mn(ZM21)BRS for tailoring both corrosion resistance and biological functions.The developed“built-up”composite film shows synergistic functionalities,allowing the compression and expansion of the coated ZM21 BRS on an angioplasty balloon without cracking or peeling.Of special importance is that the synergistic corrosion control effects of the“built-up”composite film allow for maintaining the mechanical integrity of stents for up to 3 months,where complete biodegradation and no foreign matter residue were observed about half a year after implantation in rabbit iliac arteries.Moreover,the functionalized ZM21 BRS accomplished re-endothelialization within one month.

Adhesive and Self-Healing Polyurethanes with Tunable Multifunctionality

Many polyurethanes(PUs)are blood-contacting materials due to their good mechanical properties,fatigue resistance,cytocompatibility,biosafety,and relatively good hemocompatibility.Further functionalization of the PUs using chemical synthetic methods is especially attractive for expanding their applications.Herein,a series of catechol functionalized PU(CPU-PTMEG)elastomers containing variable molecular weight of polytetramethylene ether glycol(PTMEG)soft segment are reported by stepwise polymerization and further introduction of catechol.Tailoring the molecular weight of PTMEG fragment enables a regulable catechol content,mobility of the chain segment,hydrogen bond and microphase separation of the C-PUPTMEG elastomers,thus offering tunability of mechanical strength(such as breaking strength from 1.3 MPa to 5.7 MPa),adhesion,self-healing eficiency(from 14.9%to 96.7%within 2 hours),anticoagulant,antioxidation,anti-inflammatory properties and cellular growth behavior.As cardiovascular stent coatings,the C-PU-PTMEGs demonstrate enough flexibility to withstand deformation during the balloon dilation procedure.Of special importance is that the C-PU-PTMEG-coated surfaces show the ability to rapidly scavenge free radicals to maintain normal growth of endothelial cells,inhibit smooth muscle cell proliferation,mediate inflammatory response,and reduce thrombus formation.With the universality of surface adhesion and tunable multifunctionality,these novel C-PU-PTMEG elastomers should find potential usage in artificial heart valves and surface engineering of stents.

Corrigendum to “A Versatile Surface Bioengineering StrategyBased on Mussel-Inspired and Bioclickable Peptide Mimic”

In the article titled,“A Versatile Surface Bioengineering Strategy Based on Mussel-Inspired and Bioclickable Peptide Mimic”[1],there was an error in Figure 2.In panel(e),the cell pictures of PEG after culture for 24 and 72 h were updated.The corrected figure is shown and is listed as Figure 1.